Our studies are designed to investigate selected aspects of the role of the complement system in the host's defense against infection. Four distinct, but interrelated, areas of investigation are being pursued: 1. The identification of the biochemical component of Gram-positive bacteria that is responsible for activating the alternative pathway and elucidation of the mechanism(s) by which bacteria activate the alternative pathway. 2. Studies on the reason for the deficient activation of C3-9 by bacteria in newborn sera. 3. Examination of the ability of cell wall deficient bacteria (L-phase variants) to activate the alternative pathway and the role of complement in the host's defense against L-Phase variants in vivo. 4. Identification of the defect in complement function in patients with Sicke Cell Disease.